Well, if we are going to use chemotherapy, particularly for those with anaplastic astrocytomas where we do believe that there is a role for post-radiation chemotherapy, what are the optimal drugs?
Well, there are very few data out there that gives us a lead. The best, or the only data that’s really out there, comes from a randomized trial conducted by NCOG published in 1990. It took patients with high grade astrocytomas, following external beam radiation therapy and randomized them to treatment with either treatment with single agent with BCNU or PCV. If you looked at the groups as a whole there was no significant survival advantage of time to tumor progression difference between these two treatment regimens. However, when a subgroup analysis was done they looked at the minority of patients with anaplastic astrocytoma there appeared to be a very significant survival advantage for patients treated with PCV over BCNU. And hence, the standard recommendation for patients with anaplastic gliomas to be treated with the three drug combination of procarbazine, CCNU and vincristine following standard external beam radiation. It’s important to understand that this is really the only hard data that suggests that PCV is better than BCNU. This is a subgroup analysis and it consisted of only approximately 30-40 patients, and that’s whether in fact this truly is true at this point remains unclear. Nevertheless, it’s unlikely this trial is going to be reproduced so this is the data that we are stuck with.
How about the use of standard chemotherapy at the time of recurrence? Well, if you look through the literature you will see various reports of various combinations, single agent chemotherapy trials and combination chemotherapy that give relatively high response rates. It’s important to understand that the reporting of these response rates are often very over-inflated for a number of reasons. One of the major reasons is that response criteria in the neuro-oncology community have not been agreed upon and for instance, stable disease is often considered a response in most of the literature. Canadian viagra online is a successful way to fight male impotence problems. And stable disease is often not even defined by duration of stable disease. Furthermore, many of the older trials did not have imaging modalities that were accurate. They used old brain scans or some of the older data for some of the older agents only used clinical exam as a way of assessing response.
Many of these trials did not control for steroid dose and we know steroids can certainly affect the clinical symptoms of patients as well as their imaging.
As a matter of fact, I think one has to be very critical, particularly looking at the older data in neuro-oncology. It is clear regardless of what the response rate is, that for most agents, standard chemotherapy agents in the treatment of recurrent high grade gliomas that whatever responses there are tend to be very short. Although the responders may live longer than non-responders, whatever that means, there is clearly no overall survival prolongation in patients treated with chemotherapy. Furthermore, there are few if any significant quality of life studies to suggest the role of chemotherapy. I think the one potential contradiction to this is the recent demonstration that a new drug, temozolomide, has a relatively high – approximately 37% – response rate in patients with anaplastic gliomas treated at the time of recurrence who’ve had one or fewer previous chemotherapy regimens. So temozolomide for recurrent glioma probably offers something to these patients.